The overall goal of the proposed research is to determine the influence of circulating vasopressin and central serotonin in the paradoxical sympathoinhibitory response to hypotensive hemorrhage. We have conducted preliminary studies that demonstrate a role for central serotonin in mediating the loss of sympathetic activity during severe volume depletion. Several afferent pathways have been proposed to mediate the hemorrhage- induced early "decompensatory" responses characterized by a fall in renal sympathetic activity. The signal is carried by vagal afferent sensory nerves since bilateral vagotomy, but not atropine, abolishes the response. However, investigations have failed to successfully identify the afferent stimulus that mediates renal sympathoinhibition. Here, we propose a new model that involves a central serotonergic mechanism for the release of vasopressin during hemorrhage. It is hypothesized that serotonin-dependent increases in circulating vasopressin act on receptors located on the vagal afferent perikarya to mediate the reflex renal sympathoinhibition. The proposed experiments involve the use of unique surgical and pharmacological manipulations to test the hypothesized model. The experiments are designed such that a failure to validate the model will still result in a new understanding of the mechanisms involved in mediating the initial decompensatory stage of severe hypotensive hemorrhage.